Artikel
Degeneration of retinal pigment epithelium and Bruch's membrane in LDL-receptor-deficient mice as a model of age-related macular degeneration
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Autoren
Veröffentlicht: | 22. September 2004 |
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Gliederung
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Objective
To investigate the pathogenesis of age-related macular degeneration (AMD) with respect to serum lipids in an established arteriosclerosis mouse model with low-density lipoprotein receptor deficiency (LDL-r(-)).
Methods
8-months-old mice (C57BL/6) with and without LDL-r(-) were fed a standard rodent diet or a high fat diet for two months. Animals were sacrificed and serum cholesterol levels were determined. Eyes were examined by light microscopy (LM) and transmission electron microscopy (EM).
Results
Serum cholesterol levels were significant higher in LDL-r(-) mice compared to control animals without LDL-r(-). In each group levels were even more elevated after high fat diet. Control animals did not exhibit any visible changes by LM/EM. In LDL-r(-) mice the thickness of BM increased with condensation of collagenous und elastic fibers and accumulation of lipid particles. The RPE was flattened; the basal labyrinth and apical microvilli were reduced. These changes were most pronounced in LDL-r(-) mice after high fat diet. In these animals photoreceptors showed a beginning degeneration of outer segments.
Conclusions
LDL-r(-) mice exhibited reproducible degenerative changes in BM, RPE and outer photoreceptor segments. Histologic changes appeared to correlate with serum cholesterol. The changes are similar to those seen in early AMD and may help to investigate the pathogenesis of AMD.